1c3s: Difference between revisions
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'''CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH SAHA''' | {{Structure | ||
|PDB= 1c3s |SIZE=350|CAPTION= <scene name='initialview01'>1c3s</scene>, resolution 2.5Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=SHH:OCTANEDIOIC ACID HYDROXYAMIDE PHENYLAMIDE'>SHH</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH SAHA''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1C3S is a [ | 1C3S is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3S OCA]. | ||
==Reference== | ==Reference== | ||
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors., Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP, Nature. 1999 Sep 9;401(6749):188-93. PMID:[http:// | Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors., Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP, Nature. 1999 Sep 9;401(6749):188-93. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10490031 10490031] | ||
[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: penta-coordinated zinc]] | [[Category: penta-coordinated zinc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:19:28 2008'' | ||
Revision as of 11:19, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH SAHA
OverviewOverview
Histone deacetylases (HDACs) mediate changes in nucleosome conformation and are important in the regulation of gene expression. HDACs are involved in cell-cycle progression and differentiation, and their deregulation is associated with several cancers. HDAC inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), have anti-tumour effects, as they can inhibit cell growth, induce terminal differentiation and prevent the formation of tumours in mice models, and they are effective in the treatment of promyelocytic leukemia. Here we describe the structure of the histone deacetylase catalytic core, as revealed by the crystal structure of a homologue from the hyperthermophilic bacterium Aquifex aeolicus, that shares 35.2% identity with human HDAC1 over 375 residues, deacetylates histones in vitro and is inhibited by TSA and SAHA. The deacetylase, deacetylase-TSA and deacetylase-SAHA structures reveal an active site consisting of a tubular pocket, a zinc-binding site and two Asp-His charge-relay systems, and establish the mechanism of HDAC inhibition. The residues that make up the active site and contact the inhibitors are conserved across the HDAC family. These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents.
About this StructureAbout this Structure
1C3S is a Single protein structure of sequence from Aquifex aeolicus. Full crystallographic information is available from OCA.
ReferenceReference
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors., Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP, Nature. 1999 Sep 9;401(6749):188-93. PMID:10490031
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